Analytic and diagnostic procedures in the laboratory often require the transfer of a plurality of samples, simultaneously, from one array of liquid-containing wells to another. In order to transfer, add, collect or combine liquids, various multi-transferring systems have been devised. The most commonly used is a multi-pipette which collects liquid from an array of source wells for transfer to an array of target wells, simultaneously, by application or release of application, respectively, of vacuum force. In operation, the pipette for collecting or releasing of liquid is connected to a single vacuum source provided to all the pipettes in the system so that all samples in the array of wells are collected and released at once.
In recent years, magnetic particles have been used for a variety of separation, purification, and isolation techniques in connection with chemical or biological molecules. In those techniques, a molecule is coupled to a magnetic particle capable of forming a specific binding (hereinafter “affinity binding”) with a molecule in a biological sample, which is to be isolated, purified or separated. The biological sample is then brought into contact with the magnetic particle and those biological molecules which bind to the magnetic particles are then isolated by application of a magnetic field.
Various devices have been developed to utilize such magnetic separation techniques in order to transfer the magnetic particles from one location to another. Indeed, magnetic separation technology has passed through several phases in the recent years. The first generation of magnetic separation technology used a two step separation technique involving a separation stand including a magnetic plate placed directly under a micro-plate. These thirty year old simple magnetic plates were composed of permanent magnets encapsulated in plastic which would contact the micro-plate vessels containing the magnetic particle suspensions. The magnetic particles within the suspensions would be drawn to the bottom or the inner surfaces of the wells in the micro-plate and the liquid was drawn out of the well or vessel leaving the magnetic particles behind. In general, such devices are termed “first generation magnetic separators.”
One drawback of the “first generation” separators relates to the fact that the stationary permanent magnets positioned below the micro-plates do not come into direct contact with the magnetic particles due to the thickness of the plate and vessel sides. As a result, the magnetic field applied to the individual micro-plate wells is relatively weak due to the distance between the magnetic plate and the magnetic particles and separation is, therefore, somewhat inefficient.
To overcome this drawback, the recent second generation of magnetic separators generally employ a magnetic pipette in a one step separation process, wherein a magnetic rod is inserted into the magnetic solution to capture magnetic particles. Here, magnetic particles are attracted by strong magnetic fields to the rods and then moved out of the magnetic suspension and transferred to another vessel containing fresh washing liquid or reagent solution. The rod is then demagnetized to permit detachment of the magnetic particles into the other liquid.
Such a “second generation magnetic separator” is disclosed, for example, in U.S. Pat. No. 4,292,920. This device includes a single or multi-pin arrangement, corresponding to a micro-well arrangement, which is capable of insertion into the wells of a micro-plate to attract magnetic particles by magnetic force. In one embodiment, the pin is connected to an electromagnet, and by turning the electromagnet on and off the pin becomes magnetized, or non-magnetized, respectively.
Another “second generation magnetic separator” is disclosed in U.S. Pat. No. 5,567,326, which shows an apparatus and method for separating magnetically responsive particles from a nonmagnetic test medium in which they are suspended. The device comprises a plurality of nonmagnetic pins (termed “magnetic field directing elements”) arranged in an array, and a magnet positioned normal to the array. Placing the magnet on the array of pins renders all the pins in the array magnetic thereby causing particles to be attracted to them. Removing the magnet causes the pins to become non-magnetic, and consequently the magnetic particles are released from the pins.
The drawbacks of the above “second generation separators” reside in the fact that the magnetic rods or pins come into direct contact with the magnetic particles, so that if rinsing and sterilization is required, the whole apparatus or device has to be washed. Such a procedure is expensive and time consuming. Furthermore, even where the magnetic rods are covered with disposable protective tips, the collection of particles is not efficient since some of the particles remain in the suspension due to surface tension forces. Another drawback of these devices reside in the fact that where a multi-pin device is used to collect magnetic particles from a plurality of wells, all of the pins are fixed to a movable head and travel up and down as a unit such that all of the samples from all the wells have to be collected at once in an “all or none” fashion. Thus, it is not possible to selectively collect particles from only selected wells in an array.
In U.S. Pat. No. 6,409,925, Gombinsky et al. disclose a “third generation magnetic separator.” The '925 patent discloses a device wherein each collecting pin can be independently controlled. Specifically, the disclosed magnetic rod design allows for a magnet disposed therein to be freely and independently movable up or down to thereby magnetically energize and de-energize the rod. Thus, each rod is independently magnetized regardless of the magnetization of the other rods. This unique feature permits multiple degrees of freedom (i.e., pin head movement and independent magnet movement) compared to “second generation” systems that have only one degree of freedom.
Accordingly, it would be desirable to improve upon the latest “third generation” magnetic separator technology in various ways to provide a complete control and actuation system that utilizes third generation technology. It would be further desirable to provide such a system with a selectable bottom magnet array and a combinatorial tip loader for the upper pin device.